The goal of this project is to improve the diagnosis and treatment of small cell carcinoma (SCC) of the lung by learning more about the pathobiology of this tumor. The approach is to measure tumor production of neurohypophysial principles (vasopressin (VP), oxytocin (OT), vasotocin (VT), and their associated neurophysins (HNP)) and additionally of corticotrophin-like intermediate lobe peptide (CLIP) using specific radioimmunoassays (RIAs). Other methods of analysis being performed include pulse-labeling, polyacrylamide electrophoresis and isofocusing, high-pressure liquid chromatography, affinity chromatography, cell culture, amino acid analysis, protein sequencing, and flow cytometry. It now seems likely from studies conducted thus far on plasma from patients that RIAs for HNPs and possibly also for VP, OT, and VT can be used effectively in the treatment of more than 60% of patients with SCC of the lung. Moreover, our RIAs for CLIP could extend our evaluations to include all, or almost all, patients with SCC. We will use our specific antibodies: (1)\to develop rapid immunoassays for use as even more effective tools to monitor treatment; (2)\to identify tumor cells in biopsy samples and thereby detect metastatic disease; and (3)\to locate tumors in patients by external photoscanning. The last of these applications, if successful, could lead to their eventual use in targeted therapy. The rates and mode of production/release of HNP, VP, OT, and VT will be determined in cultures of SCC. Knowledge of their rates of production/release by tumor cells in vitro might allow the amount of residual tumor to be determined in patients during treatment, while information concerning their biosynthesis, storage, and release by tumor cells could lead to a better understanding of the pathobiology of SCC and to a more rational therapy. (2)